tbuckley/cabot-search huggingface dataset:
Clinical implications for patients with discordant oncotype and MammaPrint results.
Authors: Matei P. Socoteanu, Joyce O'Shaughnessy, Kent Hoskins, Adam Brufsky, Cathy Lynne Graham, Svetislava J. Vukelja, Jamal Ghazi Misleh, Karen L. Tedesco, Rakhshanda Layeequr Rahman, June Lee, Julian Berrocal, Kamal Sharma, Albert Begas, Jennifer Crozier, Ian Grady, Nina D'Abreo, Midas M. Kuilman, Holly Nguyen, Lisa Eileen Blumencranz, M. William Audeh
Journal: Journal of Clinical Oncology (2022)

560 Background: Genomic tests provide critical information regarding risk of recurrence and inform treatment plans by identifying those patients who may safely forgo chemotherapy (CT) or shorten endocrine therapy (ET) duration. The IMPACT trial demonstrated that the 70 -gene risk of recurrence assay MammaPrint (MP) and 80-gene subtyping assay BluePrint (BP) inform treatment planning and increase physician confidence. However, not all genomic tests yield the same results. To examine consistency among genomic tests, we analyzed therapy implications for patients who received results from both MP/BP and Recurrence Score (RS). Methods: Using the FLEX cohort (NCT03053193), we examined 723 patients who received both MP/BP, and RS genomic assays. We assessed the potential clinical impact by examining the standardized reports of RS and MP/BP results. MP classified tumors as either ultralow, low, or high risk and BP further classified them as luminal, basal, or HER2. RS classified tumors as low (RS0-10), intermediate (RS11-25), or high (RS26-100). Clinical impact was defined as discordant genomic resulting in different treatment recommendations. Undertreatment indicates patients who may not have received CT based on RS but may have based on MP/BP and overtreatment those patients who would have received CT based on RS, but not based on MP/BP. ET duration too long is indicative of those patients that are ultralow risk by MP, regardless of RS classification, as those patients may have safely reduced the duration of their ET. Although outcomes are not available, treatment impacts are presuming a patient received both tests, but the treating physician opted to guide therapy according to the RS results rather than MP/BP. Results: We observed discordant results with a clinical impact in 49% (354) of patients, with 34% (244) who may be undertreated, 2% (11) potentially overtreated, and 14% (99) who may not be given the option to decrease ET to two years based on ultralow MP genomic risk. Of 114 concordant High-Risk tumors, 14% (16) were genomically Basal, and likely to require more aggressive CT than typically used in ER+ cancers. The table below summarizes the results. Conclusions: More than half of the patients in this cohort were at potential risk for undertreatment or overtreatment. The risk to patients is far more significant in the event of undertreatment, as this may result in incurable metastatic recurrence. Discordance between RS and MP/BP most often results in potential undertreatment if RS is used for treatment decision-making. Clinical trial information: NCT03053193.
EPID-05. A novel, clinically-relevant classification of pediatric CNS tumors for cancer registries using a clustering analysis
Authors: Daniel Moreira, Yichen Chen, Ibrahim Qaddoumi, Gino Cioffi, Kristin Waite, Quinn Ostrom, Carol Kruchko, Jill Barnholtz-Sloan, Meenakshi Devidas, Nickhill Bhakta
Journal: Neuro-Oncology (2022)

Abstract To accurately evaluate the burden of pediatric central nervous system (CNS) tumors, estimate resources for cancer control, and monitor outcomes, a classification system that segregates tumors into clinically relevant groups is essential. The current classification of CNS tumors included in the third revision of the International Childhood Cancer Classification does not identify key clinical groups, such as low- and high-grade gliomas. To address this need, a novel classification was embarked upon using ICD-O-3 codes, CBTRUS grouping, incidence, survival, and treatment modalities as inputs. For each ICD-O-3 code with &amp;gt;50 new cases/year in CBTRUS from 2000 to 2016, 2 clinicians reached consensus defining the efficacy of three treatment modalities: surgical resection, radiotherapy, and chemotherapy. Then, patient level 5-year overall survival (OS) times were simulated based on total incidence and 5-year OS for each code. Subsequently, 5 factors were included as potential classifiers: tumor behavior, CBTRUS sub-group, and efficacy of the three treatment modalities. A “survival tree” was developed by using partitioning. Starting with the patient cohort (root), univariate cox proportional hazards model was used to identify statistically significant (P &amp;lt; 0.05) factors. The factors with the largest hazard ratio were selected manually to create child nodes. Within each child node, the partitioning process was repeated on remaining factors until no statistically significant factor remained. This clustering yielded 4 main groups (low-, intermediate-, high-, and very high-risk tumors) and 11 subgroups, including “embryonal tumors” and “low-risk glial and glioneuronal tumors”. Further validation of the classification will be sought through a structured consensus process using multidisciplinary experts. This systematic method to develop a classification for pediatric CNS tumors will allow for more relevant estimations of outcomes and better estimation of resource utilization. Furthermore, this strategy could be replicated for other disease groups.
Management of renal cell carcinoma in transplant kidney: An individual patient data meta-analysis and evidence-based guide
Authors: F. Crocerossa, R. Autorino, I. Derweesh, U. Carbonara, F. Cantiello, R. Damiano, J. Rubio-Briones, M. Roupret, A. Breda, A. Volpe, M.C. Mir
Journal: European Urology (2022)
Questioning a Li-Fraumeni Syndrome diagnosis: Characterization of a commonly observed germline <i>TP53</i> variant, p.Arg156His.
Authors: Bita Nehoray, Alison Schwartz, Sophie Hyman, Samantha Stokes, Aleck Cervantes, Christopher Amos, Stephen B. Gruber, Judy Ellen Garber
Journal: Journal of Clinical Oncology (2022)

10612 Background: Germline pathogenic variants (PV) in the TP53 gene are associated with Li-Fraumeni syndrome (LFS). Increased use of multi-gene panel testing has identified TP53 variants suspected to have reduced penetrance, a departure from the significantly increased cancer risks expected with LFS, posing challenges in variant classification and clinical management. TP53 c.467G&gt;A (p.Arg156His), R156H, is a variant with over 250 observations across multiple laboratories with prior discordant classification. R156H was recently downgraded by laboratories from likely pathogenic (VLP) to variant of uncertain significance (VUS). Characterization of R156H to clarify clinical significance has the potential to impact care for many. Methods: R156H carriers were identified through the Li-Fraumeni &amp; TP53: Understanding &amp; Progress (LiFT UP) study ( https://liftupstudy.org ) from 2019-2022. Clinical data were collected and reviewed for phenotypic characterization and to determine whether LFS Classic and/or Chompret criteria were met, and to assign Li-Fraumeni spectrum classification (Kratz et al.). Results: Proband/family characteristics are in the Table. Twenty R156H carriers were identified in 11 families. Seventeen carriers had a personal history of cancer; 8 had a LFS core cancer. All core cancers were breast except for an astrocytoma and a pediatric sarcoma. Two breast cancer cases also carried a BRCA2 PV. The average age at first cancer diagnosis was 40.5 years (range 6-71). No families met Classic LFS criteria. One proband met Chompret criteria due to breast cancer &lt;31 years (who also carried a BRCA2 PV). Ten families were classified as attenuated LFS per Kratz et al. Conclusions: Most families in our case series did not meet LFS criteria, raising the question of appropriate clinical management and the willingness to de-escalate LFS surveillance. Our series supports the downgrade to VUS, but the presence of a few non-breast LFS core cancers warrants work to determine if R156H is a reduced penetrance PV. Recruitment of these families is ongoing through the LiFT UP study to perform segregation analyses and cancer risk estimations. This work may guide evaluation of other variants presenting similar challenges. [Table: see text]
Clinical effectiveness of SARS-CoV-2 vaccines and booster doses in patients with cancer: An analysis from the European OnCovid registry.
Authors: David J. James Pinato, Juan Aguilar-Company, Daniela Ferrante, Georgina Helen Hanbury, Mark Bower, Ramon Salazar, Matteo Lambertini, Paolo Pedrazzoli, Alvin Jun Xing Lee, Alasdair Sinclair, Sarah Townsed, Andrea Plaja, Marco Tucci, Ailsa Sita-Lumsden, Uma Mukherjee, Francesca Mazzoni, Avinash Aujayeb, Alessandra Gennari, Josep Tabernero, Alessio Cortellini
Journal: Journal of Clinical Oncology (2022)

e18725 Background: Immunogenicity and safety of SARS-CoV-2 vaccines have been widely investigated in patients (pts) with cancer. However, their effectiveness against Coronavirus disease 2019 (COVID-19) and the additional protective effect of a booster dose in this population are yet to be defined. Methods: Using OnCovid study data (NCT04393974), a European registry enrolling consecutive pts with cancer and COVID-19, we evaluated morbidity and 14 days case fatality rates (CFR 14 ) from COVID-19 in pts who were unvaccinated, vaccinated (either partially/full vaccinated but not boosted) and those who had received a third dose. Analyses were restricted to pts diagnosed between 17/11/2021 (first breakthrough infection in a boosted pt) and the 31/01/2022. Pts with unknown vaccination status were excluded. Results: By the data lock of 22/02/2022, out of 3820 consecutive pts from 36 institutions, 415 pts from 3 countries (UK, Spain, Italy) were eligible for analysis. Among them, 51 (12.3%) were unvaccinated, 178 (42.9%) were vaccinated and 186 (44.8%) were boosted. Among vaccinated pts, 26 (14.6%) were partially vaccinated (1 dose). Pts with haematological malignancies had more likely received a booster dose prior to infection (25.4% vs 13.6% and 11.8%, p = 0.02). We found no other associations between vaccination status and pts’ characteristics including sex, age, comorbidities, smoking history, tumour stage, tumour status and receipt of systemic anticancer therapy. Compared to unvaccinated pts, boosted and vaccinated pts achieved improved CFR 14 (6.8% and 7.0% vs 22.4%, p = 0.01), COVID-19-related hospitalization rates (26.1% and 20.6% vs 41.2%, p = 0.01) and COVID-19-related complications rates (14.5% and 15.7% vs 31.4%). Using multivariable Inverse Probability of Treatment Weighting (IPTW) models adjusted for sex, comorbidities, tumour status and country of origin we confirmed that boosted (OR 0.21, 95%CI: 0.05-0.89) and vaccinated pts (OR 0.19, 95%CI: 0.04-0.81) achieved improved CFR 14 compared to unvaccinated pts, whilst a significantly reduced risk of COVID-19 complications (OR 0.26, 95%CI: 0.07-0.93) was reported for vaccinated pts only. Conclusions: SARS-CoV-2 vaccines protect from COVID-19 morbidity and mortality in pts with cancer. Accounting for the enrichment of haematologic pts in the boosted group, the observation of comparable mortality outcomes between boosted and vaccinated pts is reassuring and suggests boosting to be associated with reduced mortality in more vulnerable subjects, despite evidence of adverse features in this group.
External validation of a model predicting increase in Gleason grade for men on Active Surveillance in the GAP3 consortium database
Authors: D. Nieboer, I. De Vos, L.S. Lee, P. Stricker, M. Frydenburg, A. Bjartell, J. Rubio-Briones, A. Semjonow, A. Rannikko, M. Van Hemelrijck, C.P. Pavlovich, P.R. Carroll, M.J. Roobol
Journal: European Urology (2022)
QOL-03. Beyond Survival: Clinical Rehabilitation and Functional Optimization Pearls for the Neuro-Oncologist
Authors: Nathan Rosenberg
Journal: Neuro-Oncology (2022)

Abstract Over the past decades, major advances in treatment for pediatric brain tumors have led to higher survival rates. Management including surgical resection, chemotherapy and radiation have led to prolonged survival though each comes with potential deleterious impact upon a child's level of function. While function-sparing treatments continue to be developed and utilized each year, the standard of care for many conditions leaves our patients with the potential for worsening function. The areas of mobility, activities of daily living, cognition, communication and swallow are all potentially impacted. Rehabilitation medicine specialists focus on detecting impairments, addressing them with practical interventions and improving the function our shared patients. Unfortunately, there is a worldwide scarcity of rehabilitation medicine physicians and the role of improving function often falls into the hands of the neuro-oncologist. A number of practical clinical assessments and interventions utilized by rehabilitation medicine specialists can be translated to the toolbox of the neuro-oncoligst. The aim of this presentation is to provide the neuro-oncologist with further abilities to enhance function with interventions that typically require low time investment. Topics covered will include the following: 1. What is spasticity, when is it necessary to treat and how is it treated? 2. Leg braces -- who needs them, who doesn't and what are the goals? 3. What physical exam signs can be utilized to detect peripheral neuropathy early and inform further treatment decisions with agents such as Vincristine. 4. What aspects of a gait assessment are high yield in detecting concern for clinical progression? The goal of this talk is high yield and low time investment.. It is unfortunately not applicable for a poster presentation. A minimum amount of time would be 15 minutes. If less time is available for the this presentation, a photo/video-based, rapid-fire format (similar to Tik-Tok content) could be utilized.
Effects of a yoga intervention on distress indicators among diverse women with gynecologic, gastrointestinal, and thoracic cancers.
Authors: Grace Ann Hanvey, Adaixa Padron, Elizabeth L. Kacel, Kelsey C. Bacharz, Dennie V. Jones, Frederic J. Kaye, Merry Jennifer Markham, Irene M. Estores, Sonia Mesa, Deidre B. Pereira
Journal: Journal of Clinical Oncology (2022)

12129 Background: Depression, anxiety, and fear of cancer recurrence (FCR) constitute prevalent psychological concerns necessitating further attention in developing supportive care interventions for women with gynecologic, gastrointestinal, and thoracic cancers. Recent evidence indicates that such concerns may be especially severe among underserved women of color and women affected by low-socioeconomic status (SES). The purpose of the present study is to evaluate the magnitude of changes in depression, anxiety, and FCR associated with a mindfulness-based yoga intervention among a diverse sample of women with these cancers. A second aim is to identify how changes in these concerns may differ across sociodemographic groups. Methods: Women with gynecologic ( n=86), gastrointestinal ( n=17), or thoracic ( n=20) cancers were enrolled in a group-based 10-week yoga intervention utilizing mindfulness meditation, relaxation, and gentle yoga. Prior to and following intervention, participants were administered assessments, including the Beck Depression Inventory – Second Edition (BDI-II) to measure depression, the State-Trait Anxiety Inventory (STAI) to assess anxiety, and the Fear of Cancer Recurrence Inventory (FCRI) to evaluate aspects of FCR. Mixed-linear models evaluated change in outcomes from pre- to post-intervention, with conditional models assessing the effects of age, race/ethnicity, and SES on change. Analyses were conducted prior to trial completion due to approaching accrual period termination. Results: The sample demonstrated a mean age of 58.46 ( SD=10.82) and mean SES score of 3.98 ( SD=1.55) using a 1 to 7 composite scale. Twenty-six percent of participants were of racial and/or ethnic minority status ( n=32). Significant declines in total depressive symptoms, somatic depressive symptoms, state anxiety, and psychological distress due to FCR were observed across the sample. Higher SES was associated with significantly greater reductions in total depressive symptoms and affective depressive symptoms, specifically. Women of color experienced significantly greater declines in somatic symptoms compared to non-Hispanic White women. Conclusions: This mindfulness-based yoga intervention was associated with significant reductions in depressive symptoms, state anxiety, and psychological distress related to FCR among women with gynecologic, gastrointestinal, and thoracic cancers. Higher SES and underserved race/ethnicity status moderated some of these effects. Future research should explore the efficacy of this intervention among diverse women in a randomized clinical trial context. Clinical trial information: NCT03385577.
Outcomes by BCL2 and MYC expression and rearrangements in untreated diffuse large B-cell lymphoma (DLBCL) from the POLARIX trial.
Authors: Franck Morschhauser, Yanwen Jiang, Fabrice Jardin, Alex Francisco Herrera, Laurie Helen Sehn, Charles Herbaux, Christopher Flowers, Tycel Jovelle Phillips, Armando López Guillermo, Catherine S. Magid Diefenbach, Gareth Gregory, Austin Injae Kim, Anna Maria Barbui, Sandhya Balasubramanian, Will Harris, Jamie Hirata, Joseph N. Paulson, Calvin Lee, Georg Lenz
Journal: Journal of Clinical Oncology (2022)

7517 Background: Overexpression of BCL2 and MYC, and translocation of MYC, BCL2, and BCL6, are associated with poorer outcomes in patients (pts) with DLBCL (Horn et al. Blood 2013). We previously reported progression-free survival (PFS) from POLARIX in subgroups of pts with DLBCL receiving Pola-R-CHP or R-CHOP, including pts with double expressor lymphoma (DEL; favoring Pola-R-CHP: hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.42–0.97), and double- or triple-hit lymphoma (DHL/THL; favoring R-CHOP: HR 3.81, 95% CI 0.82–17.64) (Tilly et al. NEJM 2022). In this prespecified exploratory analysis, we further analyzed immunohistochemistry (IHC) expression status of BCL2, MYC, and rearrangements (R) of BCL2, BCL6 and MYC as independent prognostic markers. We also explored the prognostic impact of DEL within treatment arms. Methods: BCL2 and MYC protein expression were assessed by IHC and identified as IHC+ (≥50% [BCL2]/≥40% [MYC]) or IHC−; MYC-R, BCL2-R, and BCL6-R were detected by fluorescence in situ hybridization (Tilly et al. NEJM, 2022). Exploratory multivariate Cox regression models were adjusted for treatment, stratification factors (IPI, bulky disease, geographic region), age &gt;60 years, cell of origin, and biomarker evaluated, as appropriate. Results: The prevalence, univariate HR, and 2-year (yr) PFS estimates of BCL2+/MYC+ and BCL2-R/ MYC-R/ BCL6-R subgroups are presented (Table) except for BCL6-R, because all 4 PFS events in this subgroup were with Pola-R-CHP. Multivariate analyses results for Pola-R-CHP vs R-CHOP in pts with BCL2+ (HR 0.60, 95% CI 0.43–0.86) and in pts with MYC+ (HR 0.63, 95% CI 0.45–0.89) were similar to results of univariate analyses. Multivariate analyses of other subgroups were not performed due to the low pt number with BCL2-R/ MYC-R/ BCL6-R. While pts with DEL treated with Pola-R-CHP had improved PFS vs pts treated with R-CHOP (HR 0.64, 0.42–0.97), the prognostic impact of DEL vs non-DEL was more pronounced with R-CHOP (univariate HR 1.53, 95% CI 1.06–2.21; multivariate HR 1.29, 95% CI 0.88–1.91) vs Pola-R-CHP (univariate HR 1.10, 95% CI 0.72–1.69; multivariate HR 1.42, 95% CI 0.89–2.28). Conclusions: Multivariate analyses support the benefit of Pola-R-CHP in pts with BCL2+ and MYC+ DLBCL. The poor prognostic impact associated with DEL appears reduced in Pola-R-CHP- vs R-CHOP-treated pts. Clinical trial information: NCT03274492. [Table: see text]
Real-world (RW) treatment patterns and clinical outcomes for chemotherapy-based regimens in first line (1L) MSI-H/dMMR metastatic colorectal cancer (mCRC).
Authors: Monica Chase, Mayur Amonkar, Nicole Myer, Tongtong Wang, Vladimir Turzhitsky, Alexander I. Spira
Journal: Journal of Clinical Oncology (2022)

e18755 Background: Until the global approval of pembrolizumab for the treatment of first line (1L) MSI-H/dMMR metastatic CRC (mCRC), newly diagnosed patients were managed with standard of care (SOC) treatments like chemotherapy with or without an EGFR/VEGF inhibitor, independent of biomarker testing or status. This study assessed the RW SOC treatment patterns and outcomes among 1L MSI-H/dMMR mCRC patients. Methods: A retrospective observational study was conducted among patients ≥18 years diagnosed with stage IV MSI-H/dMMR mCRC (index event) who received care in the US community-based Oncology Network. Eligible patients were identified between 01-Jun-2017 to 29-Feb-2020 and followed longitudinally until 31-Aug-2020, last patient record, or date of death: whichever occurred first. Baseline demographics, clinical characteristics, treatment patterns and clinical outcomes were reported descriptively. Key clinical outcomes of interest were time to treatment discontinuation (TTD), rw-progression free survival (rwPFS) and overall survival (OS). Kaplan-Meier survival analysis was conducted for all time-to-event variables. Results: 150 MSI-H/dMMR CRC patients treated in the 1L setting were included, of which 38.7% were treated with chemotherapy and 61.3% with chemotherapy + an EGFR/VEGF inhibitor. Nearly 75% of patients had an ECOG PS of 0-1, and the time from diagnosis of metastatic disease to initiation of 1L treatment was 5.2 (0.1, 1157.4) weeks. The median duration of follow-up was 12.9 (0.1, 37.1) and 16.2 (0.8, 36.2) months among patients treated with chemotherapy and chemotherapy + EGFR/VEGF inhibitors, respectively. Within the chemotherapy group, 86% received FOLFOX while 14% received FOLFIRI. Within the chemotherapy + EGFR/VEGF group, the most common regimen was FOLFOX+bevacizumab (67%). Conclusions: The totality of RW clinical outcomes in 1L MSI-h/dMMR mCRC suggest that despite the availability of chemotherapy and EGFR/VEGF inhibitors, an unmet need still exists that may be addressed with the recent availability of pembrolizumab for select patients. This data further supports the rationale for biomarker testing and personalized treatment of 1L CRC. Patient characteristics and clinical outcomes are summarized in the table.[Table: see text]